Female sex workers (FSW) who exchange sex for money in sub-Saharan Africa (SSA) have the highest global HIV burden among FSW, as high as 36.9%, yet are among the world's most underserved populations. In South Africa, it is estimated that there are up to 167,000 FSW who are at higher risk of HIV, TB and STIs than the general population. HIV prevalence among South African FSW is between 40% and 88%, significantly higher than the 14.6% HIV prevalence among women in the general population, and an estimated 20% of new HIV infections are attributed to sex work. Despite their substantial contribution to HIV incidence, insufficient attention has been given to FSW. Use of antiretroviral treatment (ART) among HIV+ FSW in South Africa is low, and FSW' interest in and demand for oral pre-exposure prophylaxis (PrEP) is unknown as real-world implementation studies are limited. Given the high HIV prevalence among FSW, and the high risk of acquiring HIV among the substantial numbers of HIV- FSW, attention to both treatment as prevention (TasP) and PrEP is warranted. FSW face myriad structural, social and individual-level barriers to HIV self-protection that contribute to high HIV prevalence and are underserved in receiving HIV prevention, care and treatment. However, little is known about how these factors influence FSW' uptake of and adherence to these drugs. Combination HIV prevention packages for FSW that augment TasP and PrEP with behavioral and structural adherence support interventions and work synergistically to maximize impact are imperative, but have not been sufficiently developed and tested. Formative research is needed to explore the acceptability of PrEP and reasons why HIV+ FSW are not initiating ART, and how best to implement and deliver ARV-based treatment and prevention to this underserved population. The Specific Aims of this R21 are to: (1) identify the structural, health system, interpersonal and individual-level barriers and facilitators that influence access to, use of and adherence to ARV-based prevention and treatment among brothel-based FSW via focus groups; (2) examine knowledge, beliefs and attitudes about ARV-based HIV prevention and treatment for FSW via in-depth qualitative interviews with health care providers, managers/owners and bouncers at brothels and hotels, and policymakers, and (3) elicit the views of FSW, health care providers and policymakers, and brothel and hotel managers/owners about approaches to increase brothel-and hotel-based FSW' access to and uptake of TasP and PrEP to guide the selection, design and evaluation of a future combination prevention. The study is closely aligned with NIH priorities, the recommendations of South Africa's National Sex Worker HIV Plan of PrEP, regular HIV testing for HIV-negative sex workers as part of combination HIV prevention and Universal Test and Treat for all FSW, the South African government's goal of initiating at least 80% of eligible people on ARVs, and UNAIDS 90-90- 90 goals.